1. Field of the Invention
This invention relates to devices and methods for controlling the electrochemistry of analyte sensors such as glucose sensors used in the management of diabetes.
2. Description of Related Art
Electrochemical measurements are widely used to determine the concentration of specific substances in fluids including biological analytes such as glucose and lactate. Maintaining the appropriate concentrations of glucose in the blood of an individual for example is extremely important for maintaining homeostasis. A concentration of glucose below the normal range, or hypoglycemia, can cause unconsciousness and lowered blood pressure, and may even result in death. A concentration of glucose at levels higher than normal, or hyperglycemia, can result in synthesis of fatty acids and cholesterol, and in diabetics, coma. The measurement of the concentration of glucose in a person's blood, therefore, has become a necessity for diabetics who control the level of blood glucose by insulin therapy.
In clinical settings, accurate and relatively fast determinations of glucose and/or lactate levels can be determined from blood samples utilizing electrochemical sensors. In a typical electrochemical sensor, the analyte diffuses from the test environment into the sensor housing through a permeable membrane to a working electrode where the analyte chemically reacts. A complementary chemical reaction occurs at a second electrode in the sensor housing known as a counter electrode. The electrochemical sensor produces an analytical signal via the generation of a current arising directly from the oxidation or reduction of the analyte at the working and counter electrodes. In addition to a working electrode and a counter electrode, an electrolytic electrochemical sensor often includes a third electrode, commonly referred to as a reference electrode. A reference electrode is used to maintain the working electrode at a known voltage or potential.
In general, the electrodes of an electrochemical sensor provide a surface at which an oxidation or a reduction reaction occurs (that is, an electrochemically active surface) to provide a mechanism whereby the ionic conduction of an electrolyte solution in contact with the electrodes is coupled with the electron conduction of each electrode to provide a complete circuit for a current. By definition, the electrode at which an oxidation occurs is the anode, while the electrode at which the “complementary” reduction occurs is the cathode. In optimal sensors, the working and counter electrode in combination produce an electrical signal that is both related to the concentration of the analyte and is sufficiently strong to provide a signal-to-noise ratio suitable to distinguish between concentration levels of the analyte over the entire range of interest.
A common type of glucose or lactate electrode sensor comprises an enzyme electrode which utilizes an enzyme to convert glucose or lactate to an electroactive product which is then analyzed electrochemically. In such glucose sensors for example, a chemical reaction at the electrode converts glucose in the presence of enzymes, such as glucose oxidase, and results in the formation of reaction products including hydrogen peroxide. In these reactions, glucose reacts with oxygen to form gluconolactone and hydrogen peroxide. A suitable electrode can then measure the formation of hydrogen peroxide as an electrical signal. The signal is produced following the transfer of electrons from the peroxide to the electrode, and under suitable conditions, the enzyme catalyzed flow of current is proportional to the glucose concentration. Lactate electrode sensors including an enzyme electrode, similarly convert lactate in the presence of enzymes, such as lactate oxidase.
With respect to glucose sensors, in typical enzyme electrodes, glucose and oxygen from blood, as well as some interferants, such as ascorbic acid and uric acid, diffuse through a primary membrane of the sensor. As the glucose, oxygen and interferants reach a second membrane, an enzyme, such as glucose oxidase, catalyzes the conversion of glucose to hydrogen peroxide and gluconolactone. The hydrogen peroxide may diffuse back through the primary membrane, or it may further diffuse through the secondary membrane to an electrode where it can be reacted to form oxygen and a proton to produce a current proportional to the glucose concentration. While numerous devices for determination of glucose and lactate have been described, most of them have some limitations with respect to sensitivity, reproducibility, speed of response, number of effective uses, and/or the range of detection.